Fibronectin matrix mimetic, Chimectin as a first-in-class therapeutic for chronic wound healing

ABSTRACT Chronic wounds have become a `silent epidemic' with health complications ranging from serious infections to limb amputations to death. In the U.S. alone, annual health care costs for treating chronic wounds are conservatively estimated at $32 billion. Treatment approaches for chronic wounds include surgical debridement, moist dressings, engineered skin substitutes, compression therapy, negative pressure therapy, skin grafts, and recombinant growth factors. Yet, none of these approaches has proven to be an efficient and effective therapy. Tissue repair occurs through a series of events mediated through interactions between various cell types and extracellular matrix (ECM) proteins. Fibronectin fibrils are a principal component of the wound ECM and play a key role in tissue formation. The Hocking lab has developed a series of soluble, recombinant fragments of fibronectin, termed “fibronectin matrix mimetics”, that “mimic” the structural and functional properties of insoluble fibronectin fibrils. Fibronectin matrix mimetics promote cell adhesion, proliferation, migration and contractility, modulate extracellular matrix composition, and induce local vasodilation - all of which contribute to effective tissue regeneration. Topical application of fibronectin matrix mimetics to full-thickness dermal wounds in diabetic mice accelerates epithelial maturation, and promotes granulation tissue deposition, remodeling, and re-vascularization. Thus, a primary target of the fibronectin matrix mimetics is chronic diabetic wounds. The goals of this project are to (i) fully characterize tissue responses to one of the fibronectin matrix mimetics, FNIII1H,8,10 (“Chimectin”) in genetically diabetic male and female mice, and (ii) test Chimectin's efficacy in a diabetic porcine dermal wound model. Results from these studies will lay the groundwork to advance Chimectin to clinical trials to test its ability to stimulate wound healing in diabetic patients.